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Order Articulavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
In addition to HA and NA, the outer lipoprotein envelope of the virus particle also contains several molecules of M2, an ion channel protein. The M2 protein is a minor component of the envelope that has been implicated in ion channel activity and efficient uncoating of incoming viruses during the infection cycle.
Antiviral therapeutics for viral infections of the central nervous system
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Recognizing that vaccination against the influenza virus is a more effective measure in reducing the burden of disease [54], specific antiviral agents are useful in the prophylaxis and treatment of infection. Influenza has been incriminated as a cause of CNS disease either by direct infection or as a cause of post-infectious encephalitis. Two specific viral proteins are targets for current therapies: the M2 protein, which is an ion channel in the viral membrane of influenza A, and neuraminidase, which is a surface glycoprotein common to both influenza A and B [55].
Amantadine and Rimantadine
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
The M2 protein is a homotetrameric protein, one of the three influenza envelope proteins (the others being the hemagglutinin [HA] and the neuraminidase [NA]), which are essential for virus replication in cell culture and in vivo (Takeda et al., 2002). Although the adamantane antivirals may inhibit replication of influenza and other viruses by interaction with other targets in the virus life cycle, these are not thought to be relevant at clinically achievable concentrations of adamantanes (Oxford and Schild, 1967; Kato and Eggers, 1969; Hay et al., 1985; Duff and Ashley, 1992; Pinto, 1992; Duff et al., 1994). Hence understanding the mechanism of action of adamantanes requires an understanding of the influenza virus life cycle and the relevance of the M2 protein in it (Pinto and Lamb, 2007).
Systems pharmacology approach to explore the mechanisms of shufeng Jiedu Capsule on treating H1N1 infection
Published in Drug Development and Industrial Pharmacy, 2023
Zhoufang Mei, Jing Zhang, Xuru Chen, Yanchao He, Jingjing Feng, Yong Du, Jindong Shi, Zhijun Jie
Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved process that allows cells to destroy misfolded or accumulated proteins, damaged organelles (such as mitochondria, peroxisomes, and endoplasmic reticulum), pathogens, etc. [19–21]. In addition, autophagy is believed to be a form of endogenous defense mechanism that allows cells to survive under the harsh conditions, including hypoxia, heat, starvation, and oxidative stress [22–24]. Previous studies indicated that the influenza A virus can induce autophagy. On the one hand, after the influenza virus infects the cell, the autophagy-lysosome pathway is activated to form autophagosomes, which encapsulate the virus and viral protein in the cytoplasm, destroying it to inhibit virus replication in the cell; on the other hand, the influenza virus M2 protein also inhibits the fusion of autophagosomes and lysosomes. At this time, the autophagosomes provide shelter for the encapsulated virus and viral protein and promote the replication of the virus in the cell [25,26].
Drugs repurposing for SARS-CoV-2: new insight of COVID-19 druggability
Published in Expert Review of Anti-infective Therapy, 2022
Sujit Kumar Debnath, Monalisha Debnath, Rohit Srivastava, Abdelwahab Omri
SID 26681509 and E64d are also CTSL inhibitors and are working on the cleavage of CTSL [40]. These drugs inhibited the pseudovirus infection in the Huh7 cell line infected with SARS-CoV-2. E64d exhibited lower toxicity than SID 26681509. Amantadine (previously approved for influenza and parkinsonism) downregulated the gene transcription of CTSL and showed an anti-pseudovirus effect in humanized mice [40]. An endosome is formed once the viral particles enter into cells. Afterward, M2 protein initiates the proton channel resulting in carrying protons into the interior of the virion. Due to the lipophilic nature, amantadine easily crosses the endosome membrane and interferes with the virion release into the cell [41]. An open-labeled, randomized clinical trial was conducted on 84 COVID-19 patients suffering from pneumonia where nafamostat mesylate was effective [42]. Developing a broad-spectrum protease inhibitor for SARS-CoV-2 is complex as proteases are expressed diversely into different tissues [43].
How far have we reached in development of effective influenza vaccine?
Published in International Reviews of Immunology, 2018
Qi Hao Looi, Jhi Biau Foo, May Teng Lim, Cheng Foh Le, Pau Loke Show
Currently, one of the most explored universal influenza vaccine biomarkers is the extracellular domain of the M2 protein (M2e). M2e attracts the interest of vaccine manufacturers and researchers, as it is relative conservation across viral strains and its linear peptide nature. The M2 protein is a tetrameric integral membrane protein that forms a minor component of the virus envelope and showed poor immunogenic property in its virion-associated form [53]. Slepushkin et al. [54] provided the earliest support for the protective nature of the anti-M2 antibody, showing that mice vaccinated with baculovirus-derived M2 were protected from lethal challenge with H1N1 and H3N2 subtype viruses. Subsequent modifications to the M2-based vaccines have included additional adjuvants and genes that improve immune function and expression of antigenicity. Although the exact mechanism of M2e-specific immunity is not understood thoroughly, preliminary data suggested that M2 antibodies function through antibody-dependent cell cytotoxicity dependent and/or Fc-macrophage interaction process [55]. Despite several proof-of-concept studies were carried out to investigate the protective effect of anti-M2e immunity in mice, ferret, and primate, results have been disappointing [56]. Nevertheless, a small phase-I trial of an M2e-flagellin conjugated vaccine has been conducted in healthy adults, with a fourfold increase in M2e titers observed [57]. A major challenge for future clinical evaluation of M2e platforms will be the determination of immune correlates of protection.